Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.

The pathogenesis of stroke is complex, with genetic risk factors as one of the main factors. The genetic variants of phosphodiesterase 4D (PDE4D) was significantly associated with the susceptibility to ischemic stroke (IS) in Caucasian population, but its association with the susceptibility to stroke in Chinese population is unclear. This article is intended to review the research on the association between PDE4D genetic variants and stroke susceptibility in Chinese population, aiming to further optimize the relevant research programs and provide reference for the prevention and treatment of stroke in China.
Humans ; Brain Ischemia/genetics* ; Genetic Predisposition to Disease ; East Asian People ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics* ; Stroke/genetics* ; Polymorphism, Single Nucleotide ; Risk Factors

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.

Objective To investigate the efficacy and toxicity of sorafenib in the treatment of advanced renal cell carcinoma. Methods From May 2007 to JUN 2009, 33 patients with advanced renal cell carcinoma were given oral sorafenib 400-600 mg twice daily. There were 23 males and 10 females in the study group. The pathological diagnosis of the primary tumors was clear cell carcinoma in 29 patients, papillary renal cell carcinoma in 2 patients, chromophobe renal cell carcinoma in 1 patient and chromophobe renal cell carcinoma mixed with clear renal cell carcinoma in 1 patient. Fifteen patients had multiple organ metastases and 18 patients had single organ metastasis. The median follow-up time was 29 weeks. Results Four (12%) patients achieved partial remission, 2 (6%) patients achieved progression disease, the remaining 27 (82%) patients achieved stable disease. Complete remission was not observed in the group. Two of the partial remission patients benefited on bone metastases. Common toxicities were skin reaction (85%), diarrhea (46%), erythra (42%), alopecia (36%), oral ulcer (18%) and hypertension (9%). Conclusions Sorafenib could be effective in controlling tumor growth. The overall effectiveness was 12%, the disease control proportion was 94% in this group and its toxicity was relatively minor and well tolerated.

AIM: To study the effect of berberine(Ber) on invasion and migration of PG cells from a high metastatic human giant lung carcinoma cell line and to explore its mechanism. METHODS: Agarose drop method was used to detect PG migration; transwell cabin with FN in lower chamber was adopted to detect PG chemotaxis. PG adhesion to FN and martrigel was detected by MTT; PG invasive ability was determined by transwell cabin covered with martrigel. Expression of MMP2/TIMP2 protein and mRNA were detected by quantitative immunocytochemical method and RT - PCR respectively. RESULTS: After PG was treated by Ber( 10 mg/L) for 24 h: 1 ) migration distance of Ber- treated PG cells was markedly shorter than that of control cells (P ＜0. 01 ) and the number of passed membrane cells towards FN was much fewer than that of control cells ( P ＜ 0. 01 ); 2) PG adhesion to FN and martrigel was inhibited remarkably by Ber compared with control PG; 3) the migration of PG cells through the martrigel -coated transwell was significantly inhibited by the addition of Ber; 4) MMP2 expression was reduced significantly(P ＜0. 01 ), while the TIMP2 expression showed up - regulating tendency, but had no differences compared with control group (P ＞ 0. 05). The MMP2/TIMP2 ratio was decreased; 5 )the MMP2 mRNA/TIMP2 mRNA ratio was decreased by Ber. CONCLUSION: Inhibition of cell migration, adhesion to ECM and invasion into ECM of tumor cells and regulation of homeostasis between MMPs and TIMPs to maintain ECM integrity may be the basic mechanism of inhibitive effect of Ber on invasion and metastasis of tumors.

AIM: To study the effect of berberine on the proliferation of human pulmonary carcinoma cells (PG cells). METHODS: The proliferation of PG cells was determined by using MTT assay. Cell cycle and apoptosis of PG cells were determined by using flow cytometry. Confocal scanning imaging system was used to assay the ROS-releasing level of PG cells. RESULTS: Berberine was shown to inhibit proliferation of PG cells directly and in a concentration-dependent manner (P

Objective To determine the effect of heat and noise on erythrocyte memb rane ATPase activities in pilots during flying. Method Twenty- four pilots per forming bombing for 3h (45～53℃, 122～97dB in the cabin) served as the su bjects . 21 ground personnel served as control (27℃ in the room). Blood samples were t aken from both groups before flying (6:00 a.m), and immediately (12:00 a.m.) and 8h (8:00 p.m.) after flying. Na+-K+ATPase, and Ca2+-Mg2+ATPase activities in erythrocyte membran e were determined with colorimetry. Result The Na+-K+ATPase activity in eryth rocyte membrane at 6:00 a.m.in pilots was higher than that in control group at the s ame time (P<0.01). The Ca2+-Mg2+ATPase activities in erythrocyte membrane at 12:00 a .m. and 8:00 p.m. in pilots were significantly higher, compared with those in co ntrol group at the same time (P<0.01). Conclusion The ATPase values obtained in our study were all within normal range, and the daytim e variation of both groups are the same. Exposure of human body to heat and noi se for long time may be harmful, the higher ATPase activity is, the more catabol ism of ATP will be. ATP exhaustion will lead to Ca2+ overload in erythrocy te thus stiffen the red cell membrane.

AIM: To observe the changes of glycemia and serum cholesterol and triglyceride in diabetic nephropathy rats and therapeutic effects of Xiaoke Keli Ji. METHODS: 3/4 nephrectomy was adopted firstly, three weeks later streptozotocin(STZ) was administered intraperitoneally to establish diabetic nephropathy model in rats. Animals were divided into four groups:model group, Xiaoke Keli Ji treatment group, positive control group and sham group. Changes of serum sugar and serum creatinine, cholesterol and triglyceride were examined at 1, 2, 3, 4, 5 weeks after STZ injection. Renal tissue samples were adopted at 6th week and studied by light microscopy. RESULTS: Model group demonstrated different degree of glomerular sclerosis. Lesions in treatment group were alleviated. Serum creatinine, serum sugar and serum cholesterol were higher at 1, 2, 3, 4, 5 weeks after STZ injection in model group than that of the sham group ( P

AIM: To investigate the mechanism of berberine’s inhibiting growth and metastasis of tumor by observing the effects of berberine on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were incubated with berberine. MTT assay and quantitative immunocytochemistry were used to detect cell proliferation and the expression of proliferation cell nuclear antigen (PCNA). Morphologic changes of apoptosis were observed by fluorescent staining, and Rhodamin123 was used to determinate mitochondrial membrane potential under the laser confocal microscopy. RESULTS: HUVEC proliferation was inhibited by co-incubating with berberine (20 mg/L) for 24 h and berberine (10 mg/L, 20 mg/L) for 48 h (P